Interstitial tissue of mammalian testes consists of a variety of cell types including Leydig cells, macrophages, fibroblasts and components of the blood and lymphatic system. In rats, testicular macrophages represent about 20% of the interstitial tissue profile in histologic sections. Functions of testicular macrophages remain unknown. Testicular macrophages are often observed in intimate association with Leydig cells, and portions of Leydig cell cytoplasm are endocytosed by macrophages. Testicular macrophages in hypophysectomized rats bind 125I-FSH and increase their production of lactate in response to FSB. Recently, we reported that interleukin-l (IL-l) is a potent inhibitor of Leydig cell steroidogenesis in primary culture. Decreased testosterone formation may contribute to catabolic effects of the acute phase response to microbial invasion. Impaired reproductive functions that occur during infection may be in part mediated by increased IL-l production. The aim of the present project is to further investigate the effects of IL-l on Leydig cell function and the interactions between macrophages and Leydig cells by: 1. Evaluating the in vivo and in vitro effects of IL-l on Leydig cell steroidogenesis. 2. Identifying IL-l receptors of Leydig cells 3. Identifying testicular IL-l by using Northern blot hybridization, in situ hybridization and immunocytochemical methods. 4. Isolating testicular macrophages. Macrophages will be stimulated with a variety of factors, such as FSH, lipopolysaccharide. and then co-cultured with Leydig cells. The effect of testicular macrophages on Leydig cell function will be evaluated.